The pharmacological function and importance of calcium antagonists, or calcium channel blockers, is well known and has been extensively reported in the literature [see; e.g., P. D. Henry, "Comparative Pharmacology of Calcium Antagonists: Nifedipine, Verapamil and Diltiazem", The American Journal of cardiology, 46, 1047-1058 (1980); K. H. Dangman, et al., "Effects of Nifedipine on Electrical Activity of Cardiac Cells", The American Journal of Cardiology, 46, 1061-1067 (1980); E. Braunwald, "Introduction: Calcium Channel Blockers", The American Journal of Cardiology, 46, 1045 (1980); L. D. Hillis, "The New Coronary Vasodilators: Calcium Blockers", J. Card. Med., 5(6), 583 (1980); M. J. Berridge, "Receptors and Calcium Signalling", Trends in Pharmacological Sciences 1, 419, (1980); W. G. Nayler, et al., "Calcium Antagonists: definition and mode of action", Basic Research in Cardiology, 76, No. 1, 1-15 (1981)].
Weller et al., [J. Org. Chem., 48, pp. 3061-7 (1983)]disclose 1'-methylspiro [benzofuran-3(2H),4'-piperidine]as a substructure of morphine which is an early intermediate in a general synthesis of morphine but not possessing exceptional analgesic activity. Weller et al. also teach the preparation of spiro[benzofuran-3(2H),4'(1'H)-pyridines]as potential intermediates in a synthesis of morphine but no biological activity of these compounds is reported.
Goldman [Angew. Chem. Int. Ed. Engl., 20, pp. 779-780 (1981)]teaches the preparation of spiro[benzothiophene-1-oxide,4'-pyridines]as an intermediate in the preparation of 4,4-disubstituted 1,4-dihydropyridines.